NEUROLOGY 1994;44:1872
© 1994 American Academy of Neurology
Familial aggregation of amyotrophic lateral sclerosis, dementia, and Parkinson's disease
Evidence of shared genetic susceptibility
Danielle Majoor-Krakauer, MD, MS,
Ruth Ottman, PhD,
William G. Johnson, MD and
Lewis P. Rowland, MD
G.H. Sergievsky Center and Epidemiology Division, School of Public Health (Drs. Majoor-Krakauer and Ottman), Columbia University, New York, NY; the Department of Clinical Genetics and Department of Epidemiology and Biostatistics (Dr. Majoor-Krakauer), University Hospital, Rotterdam, The Netherlands; the Epidemiology of Brain Disorders Research Department (Dr. Ottman), New York State Psychiatric Institute, New York, NY; the Eleanor and Lou Gehrig MDA/ALS Center (Drs. Johnson and Rowland), Neurological Institute, Columbia-Presbyterian Medical Center, New York, NY; and the Division of Neurogenetics (Dr. Johnson), Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ.
Clinicians have long suspected an association of classic amyotrophic lateral sclerosis (ALS) with Parkinson's disease (PD), dementia, or both. If proven, this would raise the possibility of a shared genetic susceptibility to the three disorders. To investigate this hypothesis, we compared 151 newly diagnosed ALS patients (seven familial) with 140 controls in terms of cumulative incidence of ALS, PD, and dementia in parents, siblings, and grandparents. We used Cox proportional hazards analysis to compute rate ratios (RRs) for ALS, dementia, and PD in relatives of ALS patients versus relatives of controls. The risk for dementia was significantly higher in relatives of ALS patients than in those of controls (RR = 1.9; 95% CI 1.1-3.1) and was similar for relatives of patients with sporadic and familial ALS. The risk of PD was higher in relatives of patients with familial ALS (RR = 5.6; 95% CI 0.6-50.3) than in relatives of patients with sporadic ALS (RR = 1.8; 95% CI 0.5-6.0), but these differences were not statistically significant, probably due to insufficient statistical power with the available sample size. These findings indicate that ALS and dementia, and perhaps also PD, co-occur within families more often than expected by chance, suggesting that there may be a shared genetic susceptibility to these disorders.
Address correspondence and reprint requests to Dr. Ruth Ottman, G.H. Sergievsky Center, Columbia University, 630 W. 168th Street, New York, NY 10032.
Supported by a grant from the Muscular Dystrophy Association.
Received August 25, 1993. Accepted in final form March 17, 1994.
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